tbuckley/cabot-search huggingface dataset:
Positive margin and advanced depth of invasion as the indicators for assessing the necessity of adjuvant chemoradiotherapy in early-stage oral cavity squamous cell carcinoma.
Authors: Hsueh-Ju Lu, Yu-Wei Chiu, Chih-Yu Peng, Hsien-Chun Tseng, Chung-Han Hsin, Chun-Yi Chuang, Chun-Chia Chen, Ming-Fang Wu, Wei-Shiou Huang, Sung-Fa Yang
Journal: Journal of Clinical Oncology (2023)

e18052 Background: Adjuvant therapy was indicated for patients with a high risk of disease progression after curative therapy, and RTOC 9501/EORTC 22931 were the landmark studies for assessing the necessity of adjuvant therapy in oral cavity squamous cell carcinoma (OCSCC). However, the role of adjuvant therapy in early-staging OCSCC, which was redefined by the 8th edition American Joint Committee on Cancer (AJCC) staging system, was unknown. Methods: A total of 485 early-staging OCSCC patients (pT1-2N0) diagnosed between Jan 2010 and Dec 2019 were retrospectively enrolled. All of them were newly diagnosed and reevaluated to meet the criteria of the 8th edition AJCC staging system. Adjuvant therapy was discussed and concluded in the combined conference of the head and neck multidisciplinary team at Chung Shan Medical University Hospital. And the enrolled patients were divided into the groups with or without adjuvant therapy. The effectiveness of adjuvant therapy and prognostic factor for locoregional recurrence-free survival (LRFS) were analyzed. Results: Nearly one-sixth (16.1%, 78/485) of the enrolled patients received adjuvant therapy. The patients with adjuvant therapy were worse in pathologic T staging ( P &lt; 0.001), histologic grade ( P &lt; 0.001), and pathologic features (depth of invasion [DOI] &gt; 4mm, P &lt; 0.001; perineural invasion, P &lt; 0.001) than those without. Positive margin and advanced DOI ( &gt; 4mm) were the independent factors for LRFS. Adjuvant therapy did not improve LRFS that the 3-year LRFS of the patients with or without adjuvant therapy were 79.7% and 81.5%, respectively ( P = 0.718)(hazard ratio [HR], 95% confidence interval [CI]: 1.10 [0.67-1.80]). However, adjuvant chemoradiotherapy (CRT) indeed prolonged LRFS in some subgroups, such as those with positive margin or advanced DOI (the subgroup with positive margin, 3-year LRFS of those with or without adjuvant therapy, 100% and 58.8%, HR[95% CI]: 0.04[0.00-267.330]; the subgroup with advanced DOI, 3-year LRFS, 83.3% and 73.1%, HR[95% CI]: 0.48[0.16-2.01]). In addition to positive margin, advanced DOI was the most critical correlation coefficient factor among the pathologic features, including pathologic T staging, perineural invasion, lymphovascular invasion, poorly differentiated, and close margin. For the patients eligible for evaluation, forty percent (40.1%, 180/439) of the patients were diagnosed with positive margins or advanced DOI and these patients might be considered to receive adjuvant CRT in the future. Conclusions: Positive margin and DOI were the most important indicators to evaluate the necessity of adjuvant CRT in early-staging OCSCC. Future warranted studies were needed.
Outcomes of <i>Helicobacter pylori</i> (HP) infection in esophageal cancer (EC): A 5-year nationwide analysis.
Authors: Sindhu Vikash, Fnu Vikash, Ansh Mehta, Fernand Bteich, Rama Al Hamed, Karun Neupane, Abdul-Hamid Bazarbachi, M Bakri Hammami, Stepan M. Esagian, Hiba Narvel, Eleftheria Atalla, Charan Thej Reddy Vegivinti, Rajvi Gor, Nishi Shah, Aditi Shastri, Ulrich G Steidl, Amit Verma, Alejandro R. Sica, Andreas Kaubisch, Sanjay Goel
Journal: Journal of Clinical Oncology (2023)

e16079 Background: EC is a fatal condition, and recent literature suggests the association of HP with esophageal adenocarcinoma. In this study, we elucidate the outcomes of HP infection in EC. Methods: This is a retrospective longitudinal study from 2016-2020, using the nationwide inpatient sample database in the United States (US). Patients with EC with and without HP infection were selected. The baseline characteristics were compared using a T-test and Chi-Square. Multivariate regression analysis was applied to estimate the outcomes (length of hospital stay (LOS), mortality, and morbidity) while adjusting for patient and hospital confounders. We used STATA Version 17.0 for data analysis. The p-value was set at p &lt; 0.05 for statistical significance. Results: In total, 69,144 patients with esophageal cancer were identified; among them, 0.3% (n= 220) had an HP infection. The highest prevalence of cases was seen in the Southern US (35.7%). The average LOS was 3.39 days (p = 0.01), and reduced mortality (p = 0.002). The Charlson comorbidity index (CCI) score was 3 or more for 74.2% (p=0.005). With regards to outcomes, 16.4% (p&lt; 0.05) had esophageal obstruction, 20.2% (p&lt; 0.05) had anemia, and 8% (p &lt; 0.01) underwent esophagectomy. However, no significant differences in the rates of hematemesis 4.4% (p=0.15), melena 2.5% (p=0.28), or esophageal perforation 1.2% (p=0.45) were reported (Table 1). When compared to patients with HP infection, no statistically significant difference was found in the outcomes. Conclusions: Our study indicates a significantly increased prevalence of EC in the southern regions of the US, which may be attributed to regional differences in lifestyle, diet, and access to healthcare. The study population was predominantly admitted with a CCI score of 3, highlighting the burden of comorbid conditions. EC patients had decreased LOS and mortality trends in the past 5 years. Moreover, EC was associated with higher rates of esophageal obstruction and anemia. However, no effect on hematemesis, melena, and esophageal perforation was appreciated, and no statistically significant difference was found in the outcomes of EC with HP infection.[Table: see text]
The impact of sodium-glucose cotransporter-2 inhibitors on the outcome of patients with colorectal adenocarcinoma.
Authors: Cho Han Chiang, Cho Hung Chiang, YUANPING HSIA, Xin Ya See, Shih-Syuan Wang, Yuan-Jen Chen, Chun-Yu Peng, Chuan-Sheng Horng, Kit Yee Wong, Aunchalee Jaroenlapnopparat, Weitao Liu, Cho Hsien Chiang, Her-Shyong Shiah, Tomas G. Neilan
Journal: Journal of Clinical Oncology (2023)

3583 Background: The mortality of colorectal cancer remains high despite the development of novel anti-neoplastic agents. Preclinical studies have shown that colorectal cancer upregulates the expression of sodium-glucose cotransporter 2 (SGLT2) channels and inhibition of these channels by SGLT2 inhibitors (SGLT2i) reduces tumor proliferation. We aimed to investigate the impact of SGLT2i on the outcome of patients with colorectal cancer. Methods: We conducted a retrospective cohort study by including all adult patients with colorectal adenocarcinoma and type 2 diabetes mellitus in two tertiary centers in Taiwan. SGLT2i and non-SGLT2i patients were matched 1:1 based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with the use of SGLT2i. Results: We identified 1347 patients with colorectal cancer and type 2 diabetes mellitus, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of OS (5-year OS: 86.2% [95% CI: 72.0-93.5] vs. 62.3% [95% CI: 50.9-71.8], p = 0.013) and PFS (5-year PFS: 76.6% [95% CI: 60.7-86.7] vs. 57.0% [95% CI: 46.2-66.4], p = 0.021). In Cox proportional hazard analyses, the use of SGLT2i was associated with a 50-70% reduction in the risk of all-cause mortality and disease progression. The rate of cancer-associated mortality was lower in the SGLT2i group (7% vs. 21%, p = 0.005). SGLT2i were not associated with an increased risk of sepsis, hypoglycemia, or acute kidney injury. We did not detect any cases of urosepsis or diabetic ketoacidosis in the SGLT2i group. Conclusions: The use of SGLT2i was associated with a higher rate of survival in colorectal cancer patients with diabetes mellitus. [Table: see text]
Therapy with metronomic cyclophosphamide (mCyc) in metastatic castrate resistant prostate cancer (mCRPC) and genomic correlates.
Authors: Nataliya Mar, Sami Dwabe, Kevin Kayvan Zarrabi, Aditya Eturi, William Kevin Kelly, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2023)

e17041 Background: Multiple historic studies demonstrated activity of mCyc in various solid tumors, including mCRPC. Low doses of oral mCyc can lead to enhanced immune stimulation by depleting regulatory T-cells. Its adverse effect profile is well established, with grade 3 and 4 toxicities being rare. In recent years, use of mCyc in mCRPC has fallen out of favor with development of novel therapies. Methods: We conducted a retrospective study of all patients with mCRPC, who received therapy with mCyc for at least 4 weeks at the University of California Irvine and Thomas Jefferson University between 6/1/17 and 1/31/23. Different oral mCyc regimens were included - 50 mg daily continuously, 50 mg daily on days 1 to 14 out of a 28-day cycle, and 250 mg daily on days 1 to 14 out of a 28-day cycle. Results: A total of 20 patients were included, from 62 to 92 years in age. At prostate cancer (PCa) diagnosis, 60.0% (12/20) had de novo metastatic disease. Duration of mCyc therapy was 4 to 41 weeks. Median number of unique PCa therapies received prior to mCyc was 4 [range: 1 to 9], with 75.0% (15/20) pretreated with taxane-based chemotherapy. 25.0% (5/20) of patients achieved a 50% drop in PSA (PSA50), while 30.0% (6/20) achieved PSA reduction but less than PSA50. 10.0% (2/20) had PSA stability without reduction, but experienced improvement in cancer-related symptoms. In those with PSA50, median duration of therapy was 16.3 weeks [range: 14 to 41]. In PSA responders, median time to PSA nadir was 7.2 weeks [range: 1 to 28]. After starting mCyc, 38.5% (5/13) of patients with any PSA or clinical response (i.e. responders) had a transient PSA rise followed by PSA decline, which is suggestive of tumor flare. In responders, 15.4% (2/13) had liver metastasis and 7.7% (1/13) had bone marrow involvement with associated cytopenias. In responders with previous prostate biopsies, 66.6% (6/9) had Gleason 9 or 10 disease. 53.8% (7/13) of responders had genomic data available with a liquid biopsy or tissue sequencing, revealing 3 patients with TP53 mutations and 1 patient with BRCA2 and RB1 co-mutations. 15.0% (3/20) of patients required dose reduction and 20.0% (4/20) dose interruption due to toxicity, with no treatment discontinuations observed. Adverse reactions leading to dose modifications included cytopenias, anorexia, fatigue, nausea, and diarrhea. Conclusions: Despite availability of novel therapeutics for mCRPC, treatment options remain limited. Recognizing the small sample size of this retrospective dataset, oral mCyc showed promising activity with a quick onset of action and a tolerable toxicity profile in heavily pretreated mCRPC patients with aggressive disease features. Given its unique mechanism of action, this provides rationale for future clinical trials, including combining mCyc with other immunomodulating agents such as PD1/PD-L1 inhibitors.
Efficacy of PARP inhibitors in patients with metastatic castration resistant prostate carcinoma: A meta-analysis of phase III randomized controlled trials.
Authors: Rushin Patel, Mosunmoluwa Oyenuga, Afoma Onyechi, Akshit Chitkara, Sara Sartaj, Mohamed G Mohamed, Zalak Patel, Mrunal Patel
Journal: Journal of Clinical Oncology (2023)

e17060 Background: PARP inhibitors effectively treat several solid tumors, regardless of the presence of BRCA mutations. Patients with castration-resistant metastatic prostate cancer become refractory to androgen deprivation therapy. PARP inhibitors were recently approved for use in prostate cancer, and have opened new avenues in prostate cancer treatment research. Methods: We systematically searched multiple databases using pre-specified search terms. We included only phase III RCTs comparing PARP inhibitors versus standard of care in patients with castration-resistant biopsy-proven metastatic prostate cancer. The outcomes studied were radiologically guided progression-free survival (PFS) and overall survival (OS). We used a random effects model via RevMan 5.4 software for statistical analysis. Results: 3 phase III RCTs met the inclusion criteria with a total of 1606 patients (PARP inhibitors = 867 patients, standard of care = 739 patients). Compared to the standard of care, PARP inhibitors showed significantly higher PFS [HR = 0.62( 95% CI, 0.49-0.78) P &lt; 0.0001]. There was no statistically significant difference in OS [HR = 0.85( 95% CI, 0.69-0.1.04) P = 0.11] between the two groups. Conclusions: The use of PARP inhibitors in patients with castration-resistant metastatic prostate cancer is associated with improved progression-free survival. No significant difference was observed in overall survival between the two groups. There is a need to study the cost-benefit analysis of using PARP inhibitors as they do not show any improvement in overall survival. [Table: see text]
Serial monitoring of ovarian cancer risk in women with adnexal mass.
Authors: Todd C. Pappas, Srinka Ghosh, Gerard P. Reilly, Ryan Phan
Journal: Journal of Clinical Oncology (2023)

e17608 Background: Monitoring of ovarian malignancy risk in indeterminate masses is typically done using TVUS and other clinical factors. No biomarkers are available to assist physicians in clinical management of benign or indeterminate adnexal mass either on initial visit or in follow-up. We recently characterized the clinical performance of a deep neural network-derived multivariate index assay (MIA3G) [1] to assess ovarian malignancy risk in retrospective and prospectively collected multi-site clinical studies. Here we present data on MIA3G serial follow-up to monitor ovarian cancer risk in women presented with adnexal mass from the prospective studies. Methods: Data are presented from ongoing multisite clinical studies in which total 924 patients presented with adnexal masses were enrolled. Follow-up visits, scheduled at clinician’s discretion, may have included imaging and blood collection. Specimens were processed for serum and run on a clinical analyzer. MIA3G score from 0-10 was calculated using seven serum biomarkers coupling with patient age and menopausal status based on previously published neural network-based algorithm. MIA3G with NPV of 99.7% (CI:99.2–99.9) was used to risk stratify the patient with an adnexal mass into low probability of malignancy or indeterminate with a validated cut off at 5.0. For this analysis, MIA3G scores were binned into the following Zones: I (0-2.49), II (2.50 -4.99) and II (5.00-10.00). Results: Of 924 enrolled patients, 538 patients had completed clinical and biomarker data on initial study draw. Of these, 145 had at least one follow-up test and 31 had at least two follow-up test. Median duration to first follow-up test was 108 d (~3.6 mon), and median duration to second follow-up test was 272 d (~9.1 mon). Follow-up in 3 MIA3G score zones at the 0 -3.6 and 3.6 - 9.1 mon interval consistently showed 88% patients within zone I remained unchanged, whereas 12% of patients moved to zones II and III. In the 0 - 3.6 mon interval, the median change in MIA3G score from I to II was 2.25 (n = 9, range 0.54 - 3.52) and from I to III was 5.92 (n = 8, range 5.08-7.62 ). In the 3.6 - 9.1 mon testing interval, the median change in MIA3G score from zone I to II was 3.11 (n = 2, range 2.75 to 3.46) and the single patient change from I to III was 6.89. Across both testing intervals, 17%-50% of patients in zone II remain unchanged while approximately 25% patients had score increase to zone III. Importantly, 50% of patients in zone III remained unchanged in the absence of clinical intervention whereas 50% had MIA3G score reduction in association with clinical management. Conclusions: These results indicate that i) the serial follow-up with MIA3G is recommended to monitor the clinical status of the adnexal mass every 3 months, ii) MIA3G score changes of &gt; 2.25 suggest clinical follow-up, and finally iii) the MIA3G is a suitable tool for the effectiveness of clinical management of adnexal mass. [1]: DOI 10.3389/fmed.2023.1102437.
Thyroid dysfunction and immune checkpoint inhibitors: Effect on survival in elderly patients.
Authors: Clelia Donisi, Andrea Pretta, Eleonora Lai, Nicole Liscia, Andrea Cadoni, Mara Persano, Stefano Mariani, Giovanna Pinna, Dario Spanu, Giorgio Saba, Marco Migliari, Marco Dubois, Francesco Atzori, Mariele Dessì, Marco Puzzoni, Valeria Pusceddu, Pina Ziranu, Clelia Madeddu, Elena Massa, Mario Scartozzi
Journal: Journal of Clinical Oncology (2023)

e24020 Background: Aging inevitably leads to an accumulation of senescent cells, and immune system cells aren't an exception. They can contribute to a pro-inflammatory state and be involved in the immune escape of cancer cells through a boosted PD-L1 expression. Immunocheckpoint inhibitors (ICIs) represent the standard of care in several cancer histotypes, and immune-related adverse events (irAEs) seem to be associated with better outcomes. ICIs represent a valid therapeutic agent in elderly patients too. However, there is a lack of data on irAEs and outcomes correlation in this subgroup of patients. This retrospective-prospective study aims to evaluate the relationship between thyroid dysfunction and progression-free survival (PFS) and overall survival (OS) in elderly patients undergoing ICIs. Methods: From January 2019 to January 2023, we retrospectively collected data from 65 elderly patients under treatment with ICIs at the Medical Oncology Unit of the University Hospital and University of Cagliari, Italy. All patients were affected by stage IV disease. The primary endpoint was PFS and the secondary endpoint was overall survival OS. Statistical analyses were performed using the MedCalc Statistical Software Version 20.216. Results: The median age was 76 (± 5,5); 15.38% were female, whereas 84.62% were male. The histologies were: melanoma (26.9%), lung cancer (48.0%), kidney cancer (15.3%), and colorectal cancer (9.8%). Compared to those without thyroid dysfunction during immunotherapy treatment, individuals with thyroid irAE had, at univariate analysis, longer median PFS (68 versus 26 months, p = 0.02, CI 95% 18.0-68.0, HR 0.29 0.10-0.83) and longer median OS (59 versus 39 months, p = 0.04, CI 95% 25.0-90.0 HR 0.50 0.25-0.99). Conclusions: In an era where biomarkers for immunotherapeutic agents are lacking, thyroid dysfunction irAE could be a predictive factor of better PFS and OS in elderly patients affected by cancer of various histology.
Incidence and survival of oropharyngeal carcinoma patients and the development of HPV-testing prevalence in North Rhine-Westphalia: A Cancer Registry analysis from 2008-2018.
Authors: Valentin Teichler, Hiltraud Kajüter, Ina Wellmann, Michael Pogorzelski, Stephan Lang, Jens Peter Klussmann, Andreas Stang, Viktor Grünwald
Journal: Journal of Clinical Oncology (2023)

e18070 Background: Oropharyngeal cancer (OPC) is caused by tobacco and alcohol or by HPV infection, which is associated with a better overall survival. A growing incidence of OPC with a decrease in other risk factors suggests a rising proportion of HPV-associated oropharyngeal carcinomas. However, regional differences exist and require further analyses. Therefore we analysed the incidence and the survival of OPC-patients and the test-rate for HPV in the largest European cancer registry in North-Rhine Westphalia (NRW), Germany. Methods: All patients diagnosed with oropharyngeal cancer (ICD-10: C01; C02.4; C05.1; C05.2; C09.0-9; C10.0-9) during 2008-2018 were included in the study. We assumed a carcinoma to be HPV-associated if either p16-IHC-test and/or HPV-DNA-PCR test was positive. In this retrospective study we analysed pseudonymized individual pathology and incidence reports collected by the cancer registry to extract our data. Five-year survival was calculated with the Kaplan-Meier Estimator. Results: A total of 10.652 cases of oropharyngeal cancer were reported in the study period. Age standardized incidence rate was 4.1 (SE 0.041) and constant over time. The majority (M:71.9%;n = 7663/W:28.1%n = 2989) of all cases were men, which is comparable to the distribution for HPV-associated OPC (M:70,3%;n = 786/W:29,7%;n = 332). 1,866 (17.5%) of OPC were tested for HPV. (M:70,4%;1314/W29,6%;552) In 2008 the test rate was 2.3% (n = 20), which increased steadily to 49.3% (n = 490) in 2018. HPV detection rate was 59,9% (n = 1118) in tested cases, which remained stable during the observation period.(M:59,8%; W:60,1%) Five-year survival was better for HPV-associated OPC (0.656; SE 0.023) than for non-HPV-associated OPC (0.430; SE 0.026) and not-HPV-tested OPC (0.468; SE 0.006). Five-year survival was slightly worse for men with OPC (0.466; SE 0.007) than for women (0.531; SE 0.011). The mean age was 63.0 (n = 10,652; HPV+Ø = 62,5; HPV-Ø = 62,7). Conclusions: In line with existing data, HPV-associated OPC achieved a better prognosis in NRW. HPV test rate increased in OPC recently, however, about 50% were still not tested. With relatively constant fractions of HPV-positive OPC in the tested group over the timespan our data does not suggest a rise in the fraction of HPV-associated OPC, which is in contrast to published data. The retrospective analyses, variance in HPV testing as well as the lack of occupational or behavioural hazards captured in the registry limit the interpretation of our data.
PARPi monotherapy as first-line maintenance following chemotherapy + bevacizumab in advanced ovarian cancer.
Authors: Fred J. Kudrik, Anupama Vasudevan, Sandy English, Mike Gart, Taofikat Oladipo, John Hartman, Laura L. Iadeluca
Journal: Journal of Clinical Oncology (2023)

e17601 Background: Chemotherapy (CT) + bevacizumab is a standard-of-care option for first-line (1L) treatment for patients with advanced ovarian cancer (AOC). Real-world approaches to 1L maintenance (1LM) treatment include, among others, bevacizumab monotherapy or switching to poly(ADP-ribose) polymerase inhibitor (PARPi) monotherapy after completing 6–9 cycles of induction CT + bevacizumab. Methods: We identified 61 patients with AOC from the US-based, deidentified Integra PrecisionQ database who received 1LM bevacizumab monotherapy (n=27) or PARPi monotherapy (n=34) after 1L CT + bevacizumab initiated between July 1, 2019, and March 31, 2021, and followed them until the data cut-off of March 31, 2022. Using the start of 1LM therapy as the index date, we examined patient characteristics, time to next treatment or death (TTNT; often used as a real-world proxy for progression-free survival), and overall survival (OS) for these two treatment groups. Results: For patients who received 1LM bevacizumab, the median age was 69 years, 89% had Eastern Cooperative Oncology Group (ECOG) performance status 0–1, 63% had Stage III disease at index, and only 1 (4%) had a recorded/documented homologous recombination deficiency (HRd)-positive tumor. Of the 34 patients who switched to 1LM PARPi monotherapy, 21 (62%) received olaparib, 12 (35%) niraparib, and 1 (3%) rucaparib. The median age of these patients was 63.5 years, 94% had ECOG performance status 0–1, 62% had Stage III disease at index date, and 47% had HRD+ tumors. For patients who switched to 1LM PARPi monotherapy, the median TTNT was 10.8 months (mo) and 97% were still alive at the 12-month mark. For patients who continued with 1LM bevacizumab, the median TTNT was 4.9 mo and 81% remained alive at the 12-month mark. Conclusions: This study suggests that switching to maintenance with PARPi monotherapy following induction CT + bevacizumab is a viable option for the treatment of AOC. A higher prevalence of HRd patients switching to PARPi monotherapy may indicate clinician preference for PARPi monotherapy in biomarker-selected subgroups, and further analysis is needed to examine which patients are most likely to benefit from switch maintenance. Funding: GSK215281. [Table: see text]